A “Reductionist” View of Cardiomyopathy Stefanie Dimmeler, Andreas M. Zeiher  Cell  Volume 130, Issue 3, Pages 401-402 (August 2007) DOI: 10.1016/j.cell.2007.07.028 Copyright © 2007 Elsevier Inc. Terms and Conditions

Figure 1 Redox Equilibrium and Cardiac Disease (A) Oxidative stress contributes to heart failure and ischemic injury. Sources of reactive oxygen species (ROS) include mitochondria and enzymes such as the NADPH and xanthine oxidases. (B) Rajasekaran et al. (2007) show that reductive stress, due to an increase in the production of reduced glutathione (GSH) and NADPH, contributes to the pathophysiology of a mouse model of human cardiomyopathy. These mice express the human mutant αB-crystallin protein (R120GCryAB), which leads to protein aggregation and cardiomyopathy. In this model, enhanced activity of glucose-6-phosphate dehydrogenase (G6PD) increases production of NADPH, the cofactor used in the conversion of glutathione disulfide (GSSG) to GSH. The mutant αB-crystallin protein also induces expression of heat shock proteins, in particular Hsp25, and of catalase and glutathione peroxidase, which decrease ROS levels. (C) Nitrosative stress, implicated in neurodegeneration, may also play a role in cardiac disease by promoting the accumulation of misfolded proteins. The transfer of a nitric oxide group to a critical cysteine thiol inactivates the molecular chaperone protein-disulfide isomerase. Nitrosative stress also targets a ubiquitin E3 ligase thereby impairing degradation of misfolded proteins by the proteasome. Cell 2007 130, 401-402DOI: (10.1016/j.cell.2007.07.028) Copyright © 2007 Elsevier Inc. Terms and Conditions